Minimization of Pain and DistressThe National Institutes of Health (NIH) has released an announcement regarding changes to the requirements of the Vertebrate Animals Section (VAS) of grant applications, cooperative agreements and contract proposals. In an effort to reduce redundancy, the VAS will no longer require:

A description of veterinary care

Justification of animal numbers

A description of euthanasia methods (please note: if the euthanasia method is not consistent with AVMA guidelines, a description is required)

These requirements, as applicable, will take effect for all grant applications except Fellowship (F series) and Training (T series) grants for due dates on or after January 25, 2016, and will take effect for all applications for due dates on or after May 25, 2016. For more detailed information regarding the changes, please visit the official announcement here.

If not consistent, describe the method and provide a scientific justification

Worksheet for the Vertebrate Animals Section (VAS)

Modified for Tufts and Tufts Medical Center IACUC protocols. Original found at NIH website.

Instructions

Typically, all of the required elements for the VAS can be addressed within 1-2 pages. The VAS must not be used to circumvent page limits. Applicants should be aware that NIH may release information contained in funded applications pursuant to a Freedom of Information Act request.

NOTE: The text in orange directs you to the section of the IACUC animal protocol where you can find the relevant information to address the question. Please note that the information may additionally be found in other sections. If you need assistance locating the relevant information in a protocol, you can contact the IACUC office.

Description of Procedures

Investigators must include a concise, complete description of the proposed procedures. While additional details may be included in the Research Strategy, a coherent, albeit brief, description of the proposed use of the animals must be provided in the VAS. The description must include sufficient detail to allow evaluation of the procedures.

Examples of the types of procedures that may be described include:

Blood collection (Section VIII C.)

Surgical procedures (Section X)

Administration of substances (Section VIII A.)

Tumor induction (Section VII, VIII E.)

Post-irradiation procedures (Section VII)

In describing the animals, investigators must provide the following information:

Species (Section IV)

Strain (Section IV, if genetically modified)

Ages

Sex

Total number of animals to be used by species (Section XIII)

Source of the animals, if dogs or cats are proposed

Justifications

Investigators must justify the use of animals in the proposed U.S. Government Principles require grantees to consider mathematical models, computer simulation, and in vitro biological systems. The justification should indicate why the research goals cannot be accomplished using an alternative model (e.g., computational, human, invertebrate, in vitro). (Section III C)

Rationale for the choice of species must be provided (e.g., advantages of the species chosen and why alternative species are not appropriate). Discuss why less highly evolved or simpler animal models are not (Section IV B)

Minimization of Pain and Distress

Investigators should identify procedures or circumstances that may result in more than momentary discomfort, distress, pain or injury. Interventions to alleviate discomfort, distress or pain should be If pharmacological agents are used, the agents may be specified by name or class. Any additional (e.g., non- pharmaceutical) means to avoid discomfort, distress, pain or injury may be briefly described, including palliative care. (Section IX A)

The manner, circumstances and duration of all post-surgical provisions and care may be (Section X #7)

If special housing is necessary following surgery or manipulations, the VAS may describe (For regulatory exceptions- Section V #6; for nonstandard from DLAM/LAMS/CBU practices- Section VI #1)

If procedures (e.g., pharmacological, surgical) might lead to severe discomfort, distress, pain or injury, indicators for humane endpoints and euthanasia (e.g., severe infection, respiratory distress, failure to eat, tumor size) may be described. (Section IX B) All of these issues are particularly important for survival surgeries (Section X B).

If multiple surgeries are proposed, these should be well justified and provisions to avoid any potential complications may be described (Section VII, or if multiple MAJOR surgeries proposed, justified in Section V#1).

Euthanasia

Investigators should state whether euthanasia will be performed and indicate if the method of euthanasia is consistent with AVMA guidelines. If consistent, no further information is needed. If it isn’t consistent, they must describe the method of euthanasia and provide scientific justification. (Section XII)

References

The guidance in this worksheet is based on Public Health Service (PHS) Policy on Humane Care and Use of Laboratory Animals (Policy) and federal requirements. The PHS Policy incorporates the standards in the Guide for the Care and Use of Laboratory Animals and the S. Government Principles for the Utilization and Care of Vertebrate Animals Used in Testing, Research and Training, and requires that euthanasia be conducted according to the AVMA Guidelines for the Euthanasia of Animals. Additional background information and references are available on the OLAW website.

Example VAS

Vertebrate Animals

Aims 1-3 will be addressed in vitro; Aim 4 will be addressed using a mouse model of ocular infection.

Description of Procedures: Male and female Balb/c mice will be used to determine if virions treated with enzyme can cause viral keratitis, and to test the in vivo efficacy of the test The studies will require 700 mice, 4 to 6 weeks old. Ocular infection is accomplished by scratching the cornea of anesthetized mice with a sterile needle and exposing the scarred portion of the cornea to inoculum. Test articles are applied directly to the scarified cornea as liquid or cream. Following inoculation and recovery, mice are monitored for 30 days. With the mice under anesthesia, the eyes will be examined at intervals, microscopically, and are flushed with medium with 2% serum to determine viral titers. Thirty days post-infection, with the mice under deep anesthesia, the trigeminal ganglia are removed aseptically for viral assay, followed immediately by euthanasia.

Justifications: The proposal is to study mechanisms for the prevention of ocular disease caused by viral infections, a leading cause of blindness in the Mice are needed for these experiments because no alternative in vitro model incorporates all elements of the mammalian ocular immune system; too little is known about this system for the development of computer simulations or for clinical studies to be considered. Mice are a well- accepted model for studying viral keratitis, assessing the virulence of viral strains, and testing the efficacy of antivirals. Mice provide several advantages over other models for these studies: a) The murine ocular immune system is similar enough to that of humans to allow extrapolation of the results; b) Their small size allows the use of smaller amounts of drugs for testing; and c) The entire mouse genome is known and easily manipulated genetically, allowing extension of the work in future genetic studies. Balb/c mice will be used because they have intermediate resistance to infection.

Minimization of Pain and Distress: Mice will be anesthetized with isoflurane (3-5%) during the infection process, when treatments are administered, and titer samples are This eliminates the need for restraint devices and topical anesthetics that would interfere with the infection and disease process. For post-procedural pain relief, we will administer buprenorphine twice daily for the duration of the experiments (i.e., approximately two weeks post-inoculation). Death is not an endpoint for the studies; the Balb/c strain was chosen because of its resiliency and resistance to this particular virus. Our goal is to avoid severe infections leading to death. Though unlikely, if an animal reacts severely, it will be euthanized, based on humane indicators (e.g., failure to groom or feed). These experiments involve no post-surgical survival animals.